SK98296A3 - Process for the preparation of arylacetic ester derivatives and intermediate products in this process - Google Patents
Process for the preparation of arylacetic ester derivatives and intermediate products in this process Download PDFInfo
- Publication number
- SK98296A3 SK98296A3 SK982-96A SK98296A SK98296A3 SK 98296 A3 SK98296 A3 SK 98296A3 SK 98296 A SK98296 A SK 98296A SK 98296 A3 SK98296 A3 SK 98296A3
- Authority
- SK
- Slovakia
- Prior art keywords
- unsubstituted
- substituted
- formula
- group
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 150000002148 esters Chemical class 0.000 title claims abstract description 11
- 239000013067 intermediate product Substances 0.000 title 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- -1 methoxyiminoacetic acid ester Chemical class 0.000 claims description 55
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 23
- 229910052763 palladium Inorganic materials 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 229910052760 oxygen Chemical group 0.000 claims description 7
- 239000001301 oxygen Chemical group 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 229910052720 vanadium Inorganic materials 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 238000009835 boiling Methods 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 2
- FAFGMAGIYHHRKN-UHFFFAOYSA-N 2-diphenylphosphanylethyl(diphenyl)phosphane;palladium Chemical compound [Pd].C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 FAFGMAGIYHHRKN-UHFFFAOYSA-N 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 claims 3
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 239000001273 butane Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims 1
- 239000000376 reactant Substances 0.000 abstract description 3
- 150000001642 boronic acid derivatives Chemical class 0.000 abstract 1
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000001624 naphthyl group Chemical group 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000000284 extract Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- USBHMYSLYGTHQY-UHFFFAOYSA-N [2-[(2-methylphenoxy)methyl]phenyl]boronic acid Chemical compound CC1=CC=CC=C1OCC1=CC=CC=C1B(O)O USBHMYSLYGTHQY-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- MYVJCOQGXCONPE-UHFFFAOYSA-N [2-(bromomethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC=C1CBr MYVJCOQGXCONPE-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- FBQZOFUQFQAKJI-UHFFFAOYSA-N methyl 2-(bromomethoxyimino)acetate Chemical compound COC(=O)C=NOCBr FBQZOFUQFQAKJI-UHFFFAOYSA-N 0.000 description 2
- JHOGJYBTAIYJOD-UHFFFAOYSA-N methyl 2-(chloromethoxyimino)acetate Chemical compound COC(=O)C=NOCCl JHOGJYBTAIYJOD-UHFFFAOYSA-N 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003461 sulfonyl halides Chemical class 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- FVFIICQSMOFGNU-UHFFFAOYSA-N (1,1-dichloro-4-diphenylphosphanylbutyl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(Cl)(Cl)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 FVFIICQSMOFGNU-UHFFFAOYSA-N 0.000 description 1
- CVTFNNJUXOBPMI-UHFFFAOYSA-N (1,2-dichloro-2-diphenylphosphanylethyl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(Cl)C(Cl)P(C=1C=CC=CC=1)C1=CC=CC=C1 CVTFNNJUXOBPMI-UHFFFAOYSA-N 0.000 description 1
- UBKCMQCDHVYUAF-UHFFFAOYSA-N (2,2-dichloro-3-diphenylphosphanylpropyl)-diphenylphosphane Chemical compound ClC(CP(C1=CC=CC=C1)C1=CC=CC=C1)(CP(C1=CC=CC=C1)C1=CC=CC=C1)Cl UBKCMQCDHVYUAF-UHFFFAOYSA-N 0.000 description 1
- MIHIJWOEDDPOLG-DUXPYHPUSA-N (2e)-2-methoxyiminoacetic acid Chemical class CO\N=C\C(O)=O MIHIJWOEDDPOLG-DUXPYHPUSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- OKVTYLOXWGCLBB-UHFFFAOYSA-N 1-bromo-2-[(2-methylphenoxy)methyl]benzene Chemical compound CC1=CC=CC=C1OCC1=CC=CC=C1Br OKVTYLOXWGCLBB-UHFFFAOYSA-N 0.000 description 1
- VIUKLTRHTPUZJV-UHFFFAOYSA-N 2-(bromomethoxyimino)acetic acid Chemical compound OC(=O)C=NOCBr VIUKLTRHTPUZJV-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- VZIRCHXYMBFNFD-IWQZZHSRSA-N 3-(2-furanyl)-2-propenal Chemical group O=C\C=C/C1=CC=CO1 VZIRCHXYMBFNFD-IWQZZHSRSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001341 alkaline earth metal compounds Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004789 chlorodifluoromethoxy group Chemical group ClC(O*)(F)F 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- BHDSUCOHNGTWEA-UHFFFAOYSA-N methyl 2-(methoxyamino)-2-oxoacetate Chemical compound CONC(=O)C(=O)OC BHDSUCOHNGTWEA-UHFFFAOYSA-N 0.000 description 1
- KLADGFFMZICZTG-UHFFFAOYSA-N methyl 2-chloro-2-methoxyiminoacetate Chemical compound CON=C(Cl)C(=O)OC KLADGFFMZICZTG-UHFFFAOYSA-N 0.000 description 1
- DOOVDXPRGGINTD-UHFFFAOYSA-N methyl 2-methoxyiminoacetate Chemical compound CON=CC(=O)OC DOOVDXPRGGINTD-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
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- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/12—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
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- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/36—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/38—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton
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- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
- C07C251/60—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by carboxyl groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/63—Carboxylic acid nitriles containing cyano groups and nitrogen atoms further bound to other hetero atoms, other than oxygen atoms of nitro or nitroso groups, bound to the same carbon skeleton
- C07C255/64—Carboxylic acid nitriles containing cyano groups and nitrogen atoms further bound to other hetero atoms, other than oxygen atoms of nitro or nitroso groups, bound to the same carbon skeleton with the nitrogen atoms further bound to oxygen atoms
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
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- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
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- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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Abstract
Description
Spôsob prípravy derivátov esterov aryloctových kyselín a medziprodukty v tomto spôsobeA process for the preparation of arylacetic acid ester derivatives and intermediates therein
Oblasť technikyTechnical field
Vynález sa týka spôsobu prípravy derivátov esterov aryloctových kyselín pomocou paládiom katalyzovanej reakcie a medziproduktov v tomto spôsobe.The invention relates to a process for the preparation of arylacetic acid ester derivatives by means of a palladium catalyzed reaction and to intermediates in the process.
Doterajší stav technikyBACKGROUND OF THE INVENTION
Spôsoby prípravy derivátov esterov metoxyiminofenyloctových kyselín nižšie uvedeného všeobecného vzorca I sú opísané V EP-A-253 123, EP-B-254 423, EP-299 694, EP-336 211, EP-354 571, EP-363 818, EP-A-525 516, EP-A-460 575, EP-A-463 488, EP-A-554 767 a ďalších zverejnených dokumentoch.Methods for the preparation of methoxyiminophenylacetic acid ester derivatives of Formula I below are described in EP-A-253,123, EP-B-254,423, EP-299,694, EP-336,211, EP-354,571, EP-363,818, EP- A-525 516, EP-A-460 575, EP-A-463 488, EP-A-554 767 and other published documents.
Podstata vynálezuSUMMARY OF THE INVENTION
Vynález sa týka nového spôsobu prípravy nesubstituovaného alebo substituovaného esteru kyseliny 2-metoxyimino-2-aryloctovej všeobecného vzorca IThe present invention relates to a novel process for the preparation of an unsubstituted or substituted 2-methoxyimino-2-arylacetic acid ester of the formula I
(I) kde v prítomnom aromatickom kruhu sa môže jedna skupina CH nahradiť atómom dusíka (pri vzniku pyridylovej skupiny) a kde dve zo štyroch väzieb kruhu, ktoré označujú prípadné substituenty, môžu v susediacej polohe predstavovať nakondenzovaný, nesubstituovaný alebo substituovaný päť- alebo šesťčlenný kruh, ktorý môže obsahovať jeden až tri rovnaké alebo rozdielne heteroatómy vybrané zo súboru zahŕňajúceho dusík, síru a kyslík, a kde(I) wherein, in the present aromatic ring, one CH group may be replaced by a nitrogen atom (to form a pyridyl group) and wherein two of the four ring bonds denoting optional substituents may represent a fused, unsubstituted or substituted five- or six-membered ring in the adjacent position , which may contain one to three identical or different heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, and wherein
R znamená alkylovú skupinu s 1 až 12 atómami uhlíka, pri ktorom saR represents an alkyl group having from 1 to 12 carbon atoms in which R @ 1 is C?
A) podrobí reakcii príslušne substituovaný dihydroxyborán všeobecného vzorca IIA) reacts an appropriately substituted dihydroxyborane of formula II
B(OH)2 B (OH) 2
alebo jeho trimérna forma všeobecného vzorca IIIor a trimeric form thereof of formula III
(III) ktorá je s ním v rovnováhe, v prítomnosti katalyzátora na báze paládia, s esterom kyseliny metoxyiminooctovej všeobecného vzorca IV(III) which is in equilibrium with it in the presence of a palladium catalyst with a methoxyiminoacetic acid ester of the formula IV
H3C n COOR V γ xH 3 C n COOR V γ x
(IV) v ktorom predstavuje alkylovú skupinu s 1 až 12 atómami uhlíka a(IV) wherein it represents an alkyl group having 1 to 12 carbon atoms and
X znamená odštiepiteľnú skupinu, alebo sa vice veršaX is a leaving group, or vice versa
B) podrobí reakcii ester kyseliny metoxyiminooctovej všeobecného vzorca XB) reacting the methoxyiminoacetic acid ester of formula X
u p N COOR 3 Vup COOR 3 V
B(ORa)2 (X) v ktorom symboly R a Rs predstavujú vždy alkylovú skupinu s 1 až 12 atómami uhlíka alebo skupina -B(OR®)2 výhodne znamená zvyšokB (OR a ) 2 (X) wherein R and R s are each C 1 -C 12 alkyl or -B (OR ®) 2 is preferably a radical
v prítomnosti katalyzátora na báze paládia, s halogénfenylovou zlúčeninou všeobecného vzorca XIin the presence of a palladium catalyst with a halophenyl compound of formula XI
(XI) ktorá je požadovaným spôsobom substituovaná, pričom Y predstavuje atóm brómu alebo jódu a štyri väzby na fenylovom kruhu predstavujú prípadné substituenty zmienené vo všeobecnom vzorci i.(XI) which is optionally substituted, wherein Y represents a bromine or iodine atom and the four bonds on the phenyl ring represent the optional substituents mentioned in formula (i).
Termín odštiepiteľná skupina označuje mukleofilný zvyšok. Ako ich príklady sa dajú uviesť napríklad atómy halogénov (napríklad chlóru, brómu alebo jódu) alebo sulfonátové zvyšky (-O-SO^-alkyl s 1 až 4 atómami uhlíka, -O-SOa-CeHs, -0-S0 -C H -CH , -0-S0 -CF atď.).The term leaving group refers to a nucleophilic residue. As examples thereof may be mentioned, for example, halogen (e.g., Cl, Br, I) or sulfonate radicals (-O-SO-alkyl of 1 to 4 carbon atoms, -O-SO-C, and E of H, -0-S0 -CH-CH, -O-SO-CF etc.).
Katalyzátor na báze paládia sa môže v zásade vybrať ľubovoľne. Dá sa použiť kovové paládium alebo paládium na uhlí. Medzi výhodné príklady patria nasledujúce zlúčeniny: Pd*XI>(0acetyl) , (fenyl P) Pd<IX>(Oacetyl) , (fenyl P) Pd<IX)Cl , (fenyl^P)4Pd<°’, bis[l,2-bis(difenylfosfino)etán]paládium<0), dichlór[1,1'-bis(difenylfosfino)ferocen]paládium*11>, dichlór[ 1,3-bis(difenylfosfino)propán]Pd *11’, dichlór[1,4-bis(difenylfosfino)bután]Pd<XX), dichlór[l,2-bis(difenylfosfino)etán]Pd*XI> a dichlórbis(trifenylfosfin)Pd*115. Na tento zoznam katalyzátorov na báze paládia sa vynález neobmedzuje.The palladium catalyst can in principle be chosen at will. Metal palladium or palladium on carbon can be used. Preferred examples include the following compounds: Pd * XI > (0acetyl), (phenyl P) Pd <IX> (Oacetyl), (phenyl P) Pd <IX) Cl, (phenyl ^ P) 4 Pd <° ', bis [ 1,2-bis (diphenylphosphino) ethane] palladium (0) , dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium * 11 >, dichloro [1,3-bis (diphenylphosphino) propane] Pd * 11 ', dichloro [1,4-bis (diphenylphosphino) butane] Pd (XX) , dichloro [1,2-bis (diphenylphosphino) ethane] Pd * XI> and dichlorobis (triphenylphosphine) Pd * 115 . The invention is not limited to this list of palladium catalysts.
Výhodné sú najmä zlúčeniny všeobecného vzorca IV a X, kde R znamená metylovú skupinu.Particularly preferred are compounds of formula IV and X, wherein R is methyl.
Presnejšie sa vynález týka spôsobu prípravy mikrobicídne a insekticídne účinnej zlúčeniny všeobecného vzorca laMore specifically, the invention relates to a process for the preparation of a microbicidally and insecticidally active compound of the formula Ia
(la) z príslušne substituovaného dihydroxybóranu všeobecného vzorca Ha(Ia) an appropriately substituted dihydroxyborane of formula IIa
B(OH)2 B (OH) 2
kdewhere
R predstavuje alkylovú skupinu s 1 až 12 atómami uhlíka, a symboly U, V, W a Z majú nižšie definovaný význam:R is C 1 -C 12 alkyl, and U, V, W and Z are as defined below:
Z znamená atóm halogénu, nitroskupinu, kyanoskupinu, nesubstituovanú alebo substituovanú alkylovú skupinu, nesubstituovanú alebo substituovanú cykloalkylovú skupinu, nesubstituovanú alebo substituovanú aralkylovú skupinu, nesubstituovanú alebo substituovanú aryloxyalkylovú skupinu, nesubstituovanú alebo substituovanú aryltioalkylovú skupinu, nesubstituovanú alebo substituovanú heteroarylalkylovú skupinu, nesubstituovanú alebo substituovanú heteroaryloxyalkylovú skupinu, nesubstituovanú alebo substituovanú heteroaryltioalkylovú skupinu, nesubstituovanú alebo substituovanú alkenylovú skupinu, nesubstituovanú alebo substituovanú aralkenylovú skupinu, nesubstituovanú alebo substituovanú aryloxyalkenylovú skupinu, nesubstituovanú alebo substituovanú aryltioalkenylovú skupinu, nesubstituovanú alebo substituovanú heteroarylalkenylovú skupinu, nesubstituovanú alebo substituovanú heteroaryloxyalkenylovú skupinu, nesubstituovanú alebo substituovanú heteroaryltioalkenylovú skupinu, nesubstituovanú alebo substituovanú alkinylovú skupinu, nesubstituovanú alebo substituovanú arylalkinylovú skupinu, nesubstituovanú alebo substituovanú heteroarylalkinylovú skupinu, nesubstituovanú alebo substituovanú arylovú skupinu, nesubstituovanú alebo substituovanú heteroarylovú skupinu, nesubstituovanú alebo substituovanú arylazoskupinu, nesubstituovanú alebo substituovanú acylaminoskupinu, skupinu -OR12, -SR13, -SOR1*, -SO_R1S, -COOR16, -CONR1VRXS, -COR19, -CR2O=NR21, -N=CR22R23, -CR24=N-OR2S, -CR25R26-O-N=CR2'7R2a, -CH2-OCOR39 alebo -NR3VR3a, pričom skupiny R12 až R2a a R3a a R39 sú rovnaké alebo rozdielne a predstavujú vždy atóm vodíka, nesubstituovanú alebo substituovanú alkylovú skupinu s 1 až 6 atómami uhlíka, nesubstituovanú alebo substituovanú alkenylovú skupinu s 1 až 6 atómami uhlíka, nesubstituovanú alebo substituovanú alkinylovú skupinu s 1 až 6 atómami uhlíka, nesubstituovanú alebo substituovanú cykloalkylovú skupinu s 3 až 6 atómami uhlíka, nesubstituovanú alebo substituovanú cykloalkylalkylovú skupinu, nesubstituovanú alebo substituovanú arylovú skupinu, nesubstituovanú alebo substituovanú heteroarylovú skupinu, nesubstituovanú alebo substituovanú aralkylovú skupinu, nesubstituovanú alebo substituovanú heteroarylalkylovú skupinu, nesubstituovanú alebo substituovanú aryloxyalkylovú skupinu, nesubstituovanú alebo substituovanú aryltioalkylovú skupinu alebo nesubstituovanú alebo substituovanú heteroaryltioalkylovú skupinu aZ is halogen, nitro, cyano, unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aralkyl, unsubstituted or substituted aryloxyalkyl, unsubstituted or substituted aryloxy or unsubstituted heteroaryl, , unsubstituted or substituted heteroarylthioalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted aralkenyl, unsubstituted or substituted aryloxyalkenyl, unsubstituted or substituted arylthioalkenyl, unsubstituted or substituted unsubstituted or substituted heteroarylalkenyl, unsubstituted or substituted heteroarylalkenyl, heteroaryltioalkenylovú, unsubstituted or substituted alkynyl, unsubstituted or substituted arylazo, unsubstituted or substituted heteroaryl-group, an unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted arylazo, unsubstituted or substituted acylamino, -OR 12, -SR 13 , -SOR 1 *, -SO 1 R 1 S , -COOR 16 , -CONR 1 IN R XS , -COR 19 , -CR 20 O = NR 21 , -N = CR 22 R 23 , -CR 24 = N-OR 2 S , - CR 25 R 26 -ON = CR 2 'R 7 2, -CH 2 -OCOR 39 or -NR 3 R 3 V, the groups R 12 to R @ 2 and R @ 3 and R @ 39 are identical or different and are hydrogen, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkenyl, unsubstituted or substituted C 1 -C 6 alkynyl carbon atoms, unsubstituted or substituted cycloalkyl having 3 to 6 carbon atoms, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted aralkyl, substituted or unsubstituted or unsubstituted or unsubstituted or substituted, , unsubstituted or substituted arylthioalkyl or unsubstituted or substituted heteroarylthioalkyl, and
R3-7 znamená atóm vodíka alebo alkylovú skupinu s 1 až 4 atómami uhlíka a symboly U, V a W sú rovnaké alebo rozdielne a predstavujú vždy atóm vodíka alebo jeden z významov uvedených pre symbol Z, alebo dve zo skupín Z, U, V a W v susediacich polohách na fenylovom kruhu spoločne s atómami uhlíka v týchto polohách tvorí nesubstituovaný alebo substituovaný päť- alebo šesťčlenný aromatický alebo cykloalifatický kruh, ktorý je nakondenzovaný na arylovy kruh a ktorý môže alebo nemusí obsahovať jeden až tri heteroatómy vybrané zo skupiny zahŕňajúcej dusík, síru a kyslík.R 3-7 represents a hydrogen atom or a C 1 -C 4 alkyl group and U, V and W are the same or different and each represents a hydrogen atom or one of the meanings given for Z or two of Z, U, V and W at adjacent positions on the phenyl ring together with the carbon atoms at these positions forms an unsubstituted or substituted five- or six-membered aromatic or cycloaliphatic ring which is fused to an aryl ring and which may or may not contain one to three heteroatoms selected from nitrogen, sulfur and oxygen.
Výhodné je pripravovať zlúčeniny všeobecného vzorca la, v ktoromIt is preferred to prepare compounds of formula Ia in which:
Z znamená skupinu -A-Rx aZ is -AR x and
-A- susediace s arylovou skupinou znamená atóm kyslíka alebo skupinu -C=C-, -CR3O=CR3X-,-A- adjacent to an aryl group means an oxygen atom or a group -C = C-, -CR 30 O = CR 3 X -,
-CHR3X-CHR30-, -CHR3XO-, -OCHR31-, -CO-O-,-CHR 3X -CHR 30 -, -CHR 3X O-, -OCHR 31 -, -CO-O-,
-CONR30-, -CHR3XS-, -CR3X=N-, -CHR3X-OCO-, -CHR3XON=CR3°-, -CR3X=N-O-, -N=CR3°-, -N=Nalebo -CHR30- a-CONR 30 -, -CH 3X S-, -CR 3X = N-, -CHR 3X -OCO-, -CHR 3X ON = CR 3 ° -, -CR 3X = NO-, -N = CR 3 ° -, -N = OR -CHR 30 - a
Rx predstavuje nesubstituovanú alebo substituovanú alkylovú skupinu, nesubstituovanú alebo substituovanú alkenylovú skupinu, nesubstituovanú alebo substituovanú alkinylovú skupinu, nesubstituovanú alebo substituovanú aralkylovú skupinu, nesubstituovanú alebo substituovanú heteroarylalkylovú skupinu, nesubstituovanú alebo substituovanú aryloxyalkylovú skupinu, nesubstituovanú alebo substituovanú heteroaryloxyalkylovú skupinu alebo heteroaryltioalkylovú skupinu alebo nesubstituovanú alebo substituovanú arylovú skupinu alebo nesubstituovanú alebo substituovanú heteroarylovú skupinu a symboly R3° a R3X sú rovnaké alebo rozdielne a znamenajú vždy priamu alebo rozvetvenú alkylovú skupinu s 1 až 4 atómami uhlíka alebo atóm vodíka.R x represents unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aralkyl, unsubstituted or substituted heteroarylalkyl, unsubstituted or substituted aryloxyalkyl or unsubstituted or unsubstituted or unsubstituted substituted aryl or unsubstituted or substituted heteroaryl; and R 3 ° and R 3X are the same or different and are in each case straight or branched (C 1 -C 4) alkyl or hydrogen.
Výhodnými zlúčeninami spadajúcimi do rozsahu všeobecného vzorca la, ktoré sa pripravujú, sú najmä zlúčeniny v ktorýchPreferred compounds within the scope of formula (Ia) to be prepared are especially those wherein:
-A- znamená skupinu -O-, -CH^-Ο-, -O-CH^-,-A- is -O-, -CH 2 -Ο-, -O-CH 2 -,
-CH ON=CR2-, -CH -, -CH -CH -, -CH=CH- alebo ' 2 7 2 2 7 -CH ON = CR 2 -, -CH -, -CH -CH -, -CH = CH- or '2 7 2 2 7
-C=C- a-C = C- a
R1 predstavuje nesubstituovanú alebo substituovanú arylovú skupinu alebo nesubstituovanú alebo substituovanú heteroarylovú skupinu aR 1 represents an unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group, and
R2 znamená atóm vodíka, alkylovú skupinu s až 4 atómami uhlíka, cykloalkylovú skupinu s 3 až 6 atómami uhlíka, trifluórmetylovú skupinu, alkoxyskupinu s 1 až 4 atómami uhlíka, alkyltioskupinu s 1 až 4 atómami uhlíka alebo alkoxyalkylovú skupinu s 1 až 4 atómami uhlíka v alkoxylovej časti a 1 až 2 atómami uhlíka v alkylovej časti, aleboR 2 is H, alkyl having up to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, trifluoromethyl, C 1 -C 4 alkyl, C 1 -C 4 alkyl or alkoxyalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to 2 carbon atoms in the alkyl moiety; or
Rx a R2 spoločne s atómom uhlíka, na ktorý sa naviazali, tvoria nesubstituovaný alebo substituovaný stvor- až sedemčlenný karbocyklický kruh, ktorý môže alebo nemusí obsahovať atóm kyslíka alebo síry a ktorý môže tiež obsahovať nesubstituovaný alebo substituovaný nakondenzovaný benzénový kruh.R x and R 2 together with the carbon to which they are bound, form an unsubstituted or substituted four- to seven-membered carbocyclic ring which may or may not contain an oxygen or sulfur atom and which may also contain an unsubstituted or substituted fused-on benzene ring.
Reakcia sa uskutočňuje v inertnom rozpúšťadle alebo zmesi rozpúšťadiel (napríklad uhľovodíka, ako je hexán, benzén, toluén alebo xylén, éteru, ako je dietyléter, dimetoxyetán alebo tetrahydrofurán, nitrilu, ako je acetonitril, amidu, ako je dimetylformamid alebo halogenovanom uhľovodíku, ako je tetrachlórmetán atď.) v prítomnosti zásady, ako sú napríklad zlúčeniny alkalických kovov alebo zlúčeniny kovov alkalických zemín, ako hydroxidy, oxidy alebo uhličitany lítia, sodíka, draslíka, horčíka, vápnika a bária v ich pevnej forme alebo vo forme vodného roztoku, a tiež oxidy, ako je oxid zinočnatý, oxid hlinitý, oxid strieborný atď. v ich pevnej forme alebo vo forme vodného roztoku. Ako príklady ďalších zásad sa môžu uviesť amíny, ako je trietylamín, pyridín, piperidín a 4-dimetylaminopyridín.The reaction is carried out in an inert solvent or solvent mixture (e.g. a hydrocarbon such as hexane, benzene, toluene or xylene, an ether such as diethyl ether, dimethoxyethane or tetrahydrofuran, a nitrile such as acetonitrile, an amide such as dimethylformamide or a halogenated hydrocarbon such as carbon tetrachloride, etc.) in the presence of a base such as alkali metal or alkaline earth metal compounds such as hydroxides, oxides or carbonates of lithium, sodium, potassium, magnesium, calcium and barium in their solid or aqueous solution, as well as oxides such as zinc oxide, alumina, silver oxide, etc. in their solid form or in the form of an aqueous solution. Examples of other bases include amines such as triethylamine, pyridine, piperidine and 4-dimethylaminopyridine.
Reakčné teploty ležia výhodne v rozmedzí od 0° C do teploty varu rozpúšťadla.The reaction temperatures are preferably in the range of 0 ° C to the boiling point of the solvent.
V mnohých prípadoch je výhodné použiť (fenyl3P)4PD<°’ ako katalyzátor, použiť toluén, dimetoxyetán, tetrahydrofurán alebo dimetylformamid ako rozpúšťadlo, použiť trietylamín, roztok hydroxidu sodného alebo roztok hydroxidu draselného, vodný uhličitan sodný alebo uhličitan draselný alebo hydrogénuhličitan sodný alebo hydrogénuhličitan draselný ako zásadu, a použiť reakčnú teplotu od 60 °C po teplotu varu reakčnej zmesi pod spätným chladičom.In many cases, it is preferred to use (phenyl 3 P) 4 PD < -1 > as a catalyst, use toluene, dimethoxyethane, tetrahydrofuran or dimethylformamide as a solvent, use triethylamine, sodium hydroxide or potassium hydroxide solution, aqueous sodium carbonate or potassium carbonate or sodium bicarbonate or potassium bicarbonate as a base, and use a reaction temperature from 60 ° C to the reflux temperature of the reaction mixture.
Nová syntéza podľa vynálezu sa vyznačuje jednoduchým postupom, ktorý poskytuje s vysokým výťažkom zlúčeniny všeobecného vzorca I alebo/a la, ktoré sa získajú vo vysoko čistej forme, a predstavuje značnú výhodu pri príprave v porovnaní so skôr opísanými spôsobmi na získanie zlúčenín všeobecného vzorca I.The novel synthesis of the invention is characterized by a simple process which provides with high yield the compounds of the formula I and / or Ia, which are obtained in highly pure form, and represents a considerable advantage in the preparation compared to the previously described methods for obtaining the compounds of the formula I.
Ako je zrejmé, má účinok ďalších substituentov na arylovom reaktante všeobecného vzorca II alebo XI v priebehu reakcie malý význam. Kľúčovým faktorom je výrazný sklon substituentov -B(OH) alebo -B(0Re)a a -X alebo Y odštiepať sa od príslušného reaktantu v prítomnosti paládia alebo/a soli paládia.As can be seen, the effect of the additional substituents on the aryl reactant of formula II or XI during the reaction is of minor importance. A key factor is the pronounced tendency of the substituents -B (OH) or -B (OR e ) and and -X or Y to cleave from the respective reactant in the presence of palladium and / or the palladium salt.
Príprava zlúčenín všeobecného vzorca II alebo všeobecného vzorca III sa uskutočňuje už známymi spôsobmi (viď R. Kôster v Houben-Weyl, zväzok 13/3a, str. 616 - 652). Zlúčeniny všeobecného vzorca XI obsahujúce odštiepiteľnú skupinu Y, ktorá sa dá ľahko odštiepiť, sú známe z literatúry a hojne opísané.The preparation of the compounds of formula II or III is carried out by methods already known (see R. Koster in Houben-Weyl, Volume 13 / 3a, pp. 616-652). Compounds of formula XI containing a cleavable group Y which are readily cleavable are known in the literature and are widely described.
Estery metoxyiminooctových kyselín všeobecného vzorca IV a všeobecného vzorca X sú nové a tvoria súčasť vynálezu. Pripravia saMethoxyiminoacetic acid esters of formula IV and X are novel and form part of the invention. They'll be ready
a) reakciou metoxyamidu všeobecného vzorca V(a) reaction of a methoxyamide of formula (V)
H_C NH COOR 3 V Y oH_C NH COOR 3 VY o
(V) s halogenačným činidlom, ako je oxychlorid fosforečný, oxybromid fosforečný, chlorid fosforečný, bromid fosforečný, tionyl chlorid, tionylbromid, fosgén, trifenylfosfín/chlorid uhličitý a trifenylfosfín/bromid uhličitý.(V) with a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, phosphorus tribromide, thionyl chloride, thionyl bromide, phosgene, triphenylphosphine / carbon tetrachloride and triphenylphosphine / carbon tetrabromide.
Výhodnými reakčnými činidlami sú oxychlorid fosforečný a oxybromid fosforečný.Preferred reagents are phosphorus oxychloride and phosphorus oxybromide.
Reakcia sa môže uskutočňovať v inertnom rozpúšťadle, ako je napríklad toluén, dimetoxyetán, dimetylformamid, 1,2-dichlóretán atď., v teplotnom rozmedzí medzi izbovou teplotou a teplotou varu rozpúšťadla. Ako rozpúšťadlo sa výhodne použije v nadbytku halogenačné činidlo a výhodne vybranou reakčnou teplotou je jeho teplota varu.The reaction may be carried out in an inert solvent such as toluene, dimethoxyethane, dimethylformamide, 1,2-dichloroethane, etc., in a temperature range between room temperature and the boiling point of the solvent. The solvent used is preferably a halogenating agent in excess, and preferably the reaction temperature selected is its boiling point.
Inak sa príprava zlúčenín všeobecného vzorca IV usku točňuje analogicky ako príprava iminohalogenidov z amidov (viď Bonnett v Patai The Chemistry of the Carbon-nitrogen Double Bond, str. 597 - 662 (Interscience Publishers, New York, 1970)).Otherwise, the preparation of compounds of formula IV is carried out analogously to the preparation of iminohalides from amides (see Bonnett in Patai, The Chemistry of the Carbon-Nitrogen Double Bond, pp. 597-662 (Interscience Publishers, New York, 1970)).
Zlúčeniny všeobecného vzorca IV, kde X predstavuje atóm jódu, sa výhodne pripraví výmenou halogénu s použitím jodidu sodného v acetóne alebo jodidu sodného v apolárnom rozpúšťadle v prítomnosti katalytického množstva chloridu železitého zo zodpovedajúcich zlúčenín všeobecného vzorca IV, kde X znamená atóm chlóru alebo brómu (viď Miller a Nunn, Tetrahedron Lett. 2691 (1974)). Príprava zlúčenín všeobecného vzorca IV, kde X predstavuje sulfonylový zvyšok, sa uskutočňuje reakciou zlúčeniny všeobecného vzorca V so zodpovedajúcim sulfonylhalogenidom. Zlúčeniny všeobecného vzorca IV sa dajú tiež pripraviťCompounds of formula IV wherein X is iodine are preferably prepared by halogen exchange using sodium iodide in acetone or sodium iodide in an apolar solvent in the presence of a catalytic amount of iron (III) chloride from the corresponding compounds of formula IV wherein X is chlorine or bromine Miller and Nunn, Tetrahedron Lett., 2691 (1974)). The preparation of compounds of formula IV wherein X is a sulfonyl radical is carried out by reacting a compound of formula V with the corresponding sulfonyl halide. Compounds of formula IV can also be prepared
b) reakciou esteru kyseliny metoxyiminooctovej všeobecného vzorca VI (VI) s halogenačným činidlom, ako je napríklad chlór alebo bróm.b) reacting a methoxyiminoacetic acid ester of formula VI (VI) with a halogenating agent such as chlorine or bromine.
Reakcia sa uskutočňuje v riedidle (napríklad vode, alkohole, éteri, uhľovodíku, prípadne halogenovanom, atď.) v teplotnom rozmedzí od 0 °C po teplotu varu riedidla, výhodne pri teplote od 0 °C do 30 °C. Zlúčeniny všeobecného vzorca V sú už známe (EP 465 986) alebo sa dajú získať už známymi spôsobmi.The reaction is carried out in a diluent (e.g. water, alcohol, ether, hydrocarbon, optionally halogenated, etc.) in the temperature range from 0 ° C to the boiling point of the diluent, preferably at 0 ° C to 30 ° C. The compounds of the formula V are already known (EP 465 986) or can be obtained by methods already known.
Sulfonátové zvyšky sú odštiepiteľné skupiny Y v zlúčeninách všeobecného vzorca XI dá získať reakciou zodpovedajúceho fenolu (Y znamená hydroxylovú skupinu) so sulfonylhalogenidom, najmä sulfonylchloridom, a najmä pokiaľ sú na fenylovom kruhu prítomné aktivujúce skupiny.The sulfonate residues are cleavable groups Y in the compounds of formula XI can be obtained by reacting the corresponding phenol (Y represents a hydroxyl group) with a sulfonyl halide, in particular a sulfonyl chloride, and especially when activating groups are present on the phenyl ring.
Zlúčeniny všeobecného vzorca VI sú buď už známe (DE 3 405 327 (1985)) alebo sa dajú analogicky pripraviť.Compounds of formula VI are either already known (DE 3 405 327 (1985)) or can be prepared analogously.
Nový spôsob podľa vynálezu sa ďalej vyznačuje:The novel process according to the invention is further characterized by:
a) použitím derivátov dihydroxybóranu, napríklad derivátov aryldihydroxybóranu, ako zložiek, ktoré sú jednoduché a sú ľahko získateľné, a tiež(a) by the use of dihydroxyborane derivatives, for example aryldihydroxyborane derivatives, as components which are simple and easy to obtain, and also
b) ľahkou získateľnosťou (s vysokými výťažkami!) a-bróm-o-tolyldihydroxybóranu, (kyseliny α-bróm-o-toluénboronovej) (Torsell, Ark. Kemi 10, 507, 509 (1957); Snyder a kol., J. Am. Chem. Soc. 80, 835 a 3611 (1958)), ktorý sa dá použiť ako medziprodukt na prípravu zlúčenín všeobecného vzorca Ha, v ktorýchb) easy recoverability (high yields) of α-bromo-o-tolyldihydroxyborane, (α-bromo-o-tolueneboronic acid) (Torsell, Ark. Kemi 10, 507, 509 (1957); Snyder et al., J. Am. Chem. Soc., 80, 835 and 3611 (1958), which can be used as an intermediate for the preparation of compounds of formula IIa in which:
Z predstavuje napríklad substituovanú alkylovú skupinu, nesubstituovanú alebo substituovanú aryloxyalkylovú skupinu, nesubstituovanú alebo substituovanú aryltioalkylovú skupinu, nesubstituovanú alebo substituovanú heteroaryloxyalkylovú skupinu, nesubstituovanú alebo substituovanú heteroaryltioalkylovú skupinu, skupinu -CR2SR26-ON=CR2VR2S alebo -CH OCOR39, a r symboly U, V a W majú vyššie definovaný význam.Z is for example substituted alkyl, unsubstituted or substituted aryloxyalkyl, unsubstituted or substituted arylthioalkyl, unsubstituted or substituted heteroaryloxyalkyl, unsubstituted or substituted heteroarylthioalkyl, -CR 2 S R 26 -ON = CR R 2 V 2 S or CH OCOR 39, and r the symbols U, V and W are as defined above.
Príklady uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION
Príklad 1Example 1
Zmes 0,8 g 2-(o-tolyloxymetyl)fenyldihydroxybóranu, 0,8 g metyl-brómmetoxyiminoacetátu, 0,38 g tetrakis(trifenylfosfin)paládia, 5 ml IM roztoku uhličitanu sodného a 15 ml toluénu sa zohrieva do varu pod spätným chladičom pri intenzívnom miešaní v atmosfére inertného plynu po dobu 6 hodín. Potom, čo zmes vychladne, sa pridá 17 ml vody a zmes sa extrahuje dvakrát etylacetátom. Zmiešané extrakty sa vysušia nad síranom sodným, roztok sa zahustí vo vákuu a zvyšok sa chromatograficky vyčistí na silikagéle s použitím zmesi dietyléteru a hexánu v objemovom pomere 1 : 2 ako elučného činidla. Týmto spôsobom sa získa 0,4 g a-metoxyimino-2-(o-tolyloxymetyl)fenylacetátu vo forme bielych kryštálov s teplotou topenia 99 - 100 °C.A mixture of 0.8 g of 2- (o-tolyloxymethyl) phenyldihydroxyborane, 0.8 g of methyl bromomethoxyiminoacetate, 0.38 g of tetrakis (triphenylphosphine) palladium, 5 ml of 1M sodium carbonate solution and 15 ml of toluene is heated to reflux. vigorous stirring under an inert gas atmosphere for 6 hours. After the mixture has cooled, water (17 ml) is added and the mixture is extracted twice with ethyl acetate. The combined extracts were dried over sodium sulfate, the solution was concentrated in vacuo and the residue purified by chromatography on silica gel using diethyl ether / hexane (1: 2 by volume) as eluent. 0.4 g of α-methoxyimino-2- (o-tolyloxymethyl) phenylacetate is thus obtained in the form of white crystals, m.p. 99-100 ° C.
Príklad 2Example 2
Príprava medziproduktuPreparation of intermediate
K roztoku 8,0 g l-bróm-2-(o-tolyloxymetyl)benzénu v 50 ml tetrahydrofuránu ochladenému na teplotu -75 °C sa pri miešaní v atmosfére dusíka po kvapkách pridá 20 ml 1,6M roztoku n-butyllítia v hexáne takou rýchlosťou, že teplota nepresiahne -70 °C. Po uplynutí ďalšej hodiny sa pri teplote -75 °C po kvapkách pridá 5,4 ml trietylborátu. Zmes sa mieša po dobu ďalších 3 hodín, potom sa pridá 5 ml nasýteného roztoku chloridu amónneho a odstráni sa chladiaci kúpeľ. Pri izbovej teplote sa pridá 100 ml IN roztoku kyseliny chlorovodíkovej a olej, ktorý sa oddelí, sa extrahuje dvakrát dietyléterom. Zmiešané éterické extrakty sa premyjú vodou a vysušia nad síranom sodným. Biela pevná látka, ktorá zvýši po odstránení rozpúšťadla destiláciou, sa vyčistí rozpustením v 2N vodnom roztoku hydroxidu sodného, roztok sa dvakrát extrahuje dietyléterom a extrakty sa potom okyslia koncentrovaným roztokom kyseliny chlorovodíkovej. Zrazenina sa odfiltruje a vysuší, čím sa získa 4,1 g 2-(o-tolyloxymetyl)fenyldihydroxybóranu vo forme bieleho prášku s teplotou topenia 170 - 171 °C.To a solution of 8.0 g of 1-bromo-2- (o-tolyloxymethyl) benzene in 50 ml of tetrahydrofuran cooled to -75 ° C is added dropwise 20 ml of a 1.6 M solution of n-butyllithium in hexane under stirring under nitrogen. at a rate such that the temperature does not exceed -70 ° C. After an additional hour, 5.4 ml of triethyl borate is added dropwise at -75 ° C. The mixture is stirred for an additional 3 hours, then 5 ml of saturated ammonium chloride solution are added and the cooling bath is removed. 100 ml of 1N hydrochloric acid solution are added at room temperature and the oil which is separated is extracted twice with diethyl ether. The combined ether extracts were washed with water and dried over sodium sulfate. The white solid which, after removal of the solvent by distillation, was purified by dissolution in 2N aqueous sodium hydroxide solution, the solution was extracted twice with diethyl ether, and the extracts were then acidified with concentrated hydrochloric acid. The precipitate was filtered off and dried, yielding 4.1 g of 2- (o-tolyloxymethyl) phenyldihydroxyborane as a white powder, m.p. 170-171 ° C.
Príklad 3Example 3
Príprava medziproduktuPreparation of intermediate
Zmes 4,9 g a-brómtolyldihydroxybóranu, 2,16 g o-krezolu, 6,4 g uhličitanu draselného, 0,1 g jodidu draselného, 2,5 ml vody a 25 ml acetonitrilu sa pri miešaní zohrieva do varu pod spätným chladičom po dobu 16 hodín. Zmes sa ochladí a preflitruje, filtrát sa zahustí vo vákuu, okyslí sa IN kyselinou chlorovodíkovou a extrahuje sa dvakrát etylacetátom. Zmiešané a vysušené extrakty sa zahustia vo vákuu a zvyšok sa chromatograficky vyčistí na silikagéle s použitím zmesi dietyléteru a hexánu v objemovom pomere 50 : 50 ako elučného činidla. Týmto spôsobom sa získa 1 g 2-(o-tolyloxymetyl)fenyldihydroxybóranu, ktorého ^H-NMR spektrum je rovnaké ako spektrum dihydro xybóranu z príkladu 2.A mixture of 4.9 g of .alpha.-bromotolyldihydroxyborane, 2.16 g of o-cresol, 6.4 g of potassium carbonate, 0.1 g of potassium iodide, 2.5 ml of water and 25 ml of acetonitrile is heated to reflux while stirring. for 16 hours. The mixture was cooled and filtered, the filtrate was concentrated in vacuo, acidified with 1N hydrochloric acid and extracted twice with ethyl acetate. The combined and dried extracts were concentrated in vacuo and the residue purified by chromatography on silica gel using diethyl ether / hexane (50/50; v / v) as eluent. In this way 1 g of 2- (o-tolyloxymethyl) phenyldihydroxyborane is obtained, the @ 1 H-NMR spectrum of which is identical to that of the dihydroxyborane of Example 2.
Príklad 4Example 4
Príprava medziproduktuPreparation of intermediate
POCI3 NIGHTS 3
Zmes 26,6 g metyl-N-metoxyoxamátu a 0,5 g dimetylformamidu v 100 ml oxychloridu fosforečného sa zohrieva do varu pod spätným chladičom po dobu 18 hodín. Po odstránení nadbytku oxychloridu fosforečného destiláciou sa zvyšok vyleje do ľadovej vody a žltý olej, ktorý sa oddelí, sa extrahuje dvakrát dietyléterom. Zmiešané extrakty sa premyjú vodou, vysušia sa nad síranom sodným a rozpúšťadlo sa odstráni destiláciou. Týmto spôsobom sa získa 24,6 g metyl-chlórmetoxyiminoacetátu vo forme bledožltých kryštálov s teplotou topenia 43 - 44 °C.A mixture of 26.6 g of methyl N-methoxyoxamate and 0.5 g of dimethylformamide in 100 ml of phosphorus oxychloride is heated to reflux for 18 hours. After removal of the excess phosphorus oxychloride by distillation, the residue was poured into ice water and the yellow oil which separated was extracted twice with diethyl ether. The combined extracts were washed with water, dried over sodium sulfate and the solvent removed by distillation. 24.6 g of methyl chloromethoxyiminoacetate are obtained in the form of pale yellow crystals, m.p. 43-44 ° C.
Metyl-brómmetoxyiminoacetát (bledožlté kryštály s teplotou topenia 49 - 51 °C) sa pripravia analogicky s použitím oxybromidu fosforečného.Methyl bromomethoxyiminoacetate (pale yellow crystals, mp 49-51 ° C) was prepared analogously using phosphorus oxybromide.
Príklad 5Example 5
Príprava medziproduktuPreparation of intermediate
Do zmesi 2,9 g metyl-metoxyiminoacetátu a 20 ml vody sa pri teplote 10 - 15 °C po dobu 1 hodiny zavádza plynný chlór. Zmes sa potom mieša pri teplote 25 - 30 °C po dobu 5 hodín a extrahuje sa dichlórmetánom. Organická fáza sa vysuší nad síranom sodným. Po odstránení rozpúšťadla destiláciou sa získaChlorine gas was introduced into the mixture of 2.9 g of methyl methoxyiminoacetate and 20 ml of water at 10-15 ° C for 1 hour. The mixture was then stirred at 25-30 ° C for 5 hours and extracted with dichloromethane. The organic phase is dried over sodium sulfate. After removal of the solvent by distillation, it is obtained
2,4 g metyl-chlórmetoxyiminoacetátu vo forme bledožltých kryštálov s teplotou topenia 43 - 44 °C.2.4 g of methyl chloromethoxyiminoacetate in the form of pale yellow crystals, m.p. 43-44 ° C.
Príklad 6Example 6
Prípravapreparation
1,58 g fenyldihydroxybóranu a 1,52 g metyl-2-chlór-2-metoxyiminoacetátu sa rozpustí v zmesi 15 ml toluénu a 4 ml etanolu a pri miešaní sa pridá 0,27 g bis(trifenylfosfín)paládiumcxx5-dichloridu a 7,5 ml IM roztoku uhličitanu sodného, pričom sa pôvodne žltá suspenzia zafarbí na červeno. Zmes sa mieša počas pol hodiny pri izbovej teplote, potom jednu hodinu pri teplote 45 °C a ďalšiu hodinu pri teplote 50 °C. Zmes sa ochladí na izbovú teplotu, potom sa pridá 20 ml vody a toluénová fáza sa oddelí. Vodná fáza sa extrahuje dvakrát 40 ml etylacetátu a zmiešané organické extrakty sa prefiltrujú cez vrstvu kremeliny. Filtrát sa premyje 20 ml vody, vysuší sa nad síranom sodným a zahustí odparením. Získa sa 1,7 g červenohnedého oleja, ktorý sa vyčistí na stĺpci silikagélu s použitím zmesi etyléteru a hexánu v pomere 1 : 4 ako elučného činidla. Výťažok tvorí 0,65 g (43,9 % teoretického).1.58 g of phenyldihydroxyborane and 1.52 g of methyl 2-chloro-2-methoxyiminoacetate are dissolved in a mixture of 15 ml of toluene and 4 ml of ethanol, and 0.27 g of bis (triphenylphosphine) palladium cxx5- dichloride and 7, 5 ml of 1M sodium carbonate solution, the original yellow suspension turning red. The mixture was stirred for half an hour at room temperature, then one hour at 45 ° C and another hour at 50 ° C. The mixture is cooled to room temperature, then 20 ml of water are added and the toluene phase is separated. The aqueous phase is extracted twice with 40 ml of ethyl acetate and the combined organic extracts are filtered through a pad of diatomaceous earth. The filtrate is washed with 20 ml of water, dried over sodium sulphate and concentrated by evaporation. 1.7 g of a red-brown oil are obtained which is purified on a silica gel column using a 1: 4 mixture of ethyl ether and hexane as eluent. Yield: 0.65 g (43.9% of theory).
Oximétery všeobecného vzorca VII sa dajú pripraviť analogicky k vyššie uvedeným príkladom z dihydroxybóranu všeobecného vzorca Ilb a metyl-chlór- alebo brómmetoxyiminoacetátu v prítomnosti katalyzátora na báze paládia.The oximethers of formula VII can be prepared analogously to the above examples from dihydroxyborane of formula IIb and methyl chloro or bromomethoxyiminoacetate in the presence of a palladium catalyst.
Tabulka 1Table 1
Medziprodukty všeobecného vzorca IlbIntermediates of formula IIb
B(OH)2 B (OH) 2
(VII)(VII)
Vyššie uvedené medziprodukty všeobecného vzorca Ilb z tabuľky 1 sú ďalším predmetom vynálezu.The above intermediates of formula IIb of Table 1 are a further object of the invention.
Tabulka 2Table 2
Oximétery všeobecného vzorca VIII sa dajú pripraviť analogicky ako v príklade 1 z dihydroxybóranu všeobecného vzorca líc a esteru kyseliny metoxyiminooctovej všeobecného vzorca IV v prítomnosti katalyzátora na báze paládia, pričom oximétery všeobecného vzorca VIII sú charakterizované ich teplotou topenia (t.t.) alebo/a hmotnostnou spektrometriou (M* (intenzita v %), základný pik):The oximethers of formula VIII can be prepared analogously to Example 1 from the dihydroxyborane of formula IIc and the methoxyiminoacetic acid ester of formula IV in the presence of a palladium catalyst, the oximethers of formula VIII being characterized by their melting point (tt) and / or mass spectrometry ( M * (intensity in%), basic peak):
Pokračovanie tabulky 2Continuation of Table 2
Pokračovanie tabuľky 2Continuation of Table 2
ee
Pokračovanie tabuľky 2Continuation of Table 2
Pokračovanie tabuľky 2 príklad R2 Continuation of Table 2 Example R 2
fyzikálne údajephysical data
CH, 3-difluórmetoxyfenyl t.t. βο-69 ’CCH, 3-difluoromethoxyphenyl m . t . βο-69 ° C
t.t. 108-110 ’Cmp 108-110 ’C
t.t. 92-94 ’Cmp 92-94 ’C
t.t. 108-110 ’Cmp 108-110 ’C
t.t. 98-101 ’Cmp 98-101 ’C
t.t. 89-92 ’Cmp 89-92 ’C
t.t. 124-127 ’Cmp 124-127 ’C
t.t. 82-86 ’Cmp 82-86 ’C
Pokračovanie tabuľky 2 príklad R2 Continuation of Table 2 Example R 2
fyzikálne údajephysical data
100100
t.t. 118-120 °C t-t. 97-104 eCmp 118-120 ° C mp. 97-104 e C
386 (13); 116386 (13); 116
Vyššie uvedené medziprodukty všeobecného vzorca líc z tabuľky 2 sú ďalším predmetom vynálezu, najmä tie, v ktorýchThe above intermediates of formula IIc of Table 2 are a further object of the invention, in particular those in which:
Rx predstavuje až trisubstituovaný fenylový kruh aR x represents up to trisubstituted phenyl ring a
R2 znamená alternatívne metylovú skupinu, etylovú skupinu, trifluórmetylovú skupinu, cyklopropylovú skupinu, metoxyskupinu alebo metyltioskupinu. R2 is alternatively methyl, ethyl, trifluoromethyl, cyclopropyl, methoxy or methylthio.
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| TR199700975A2 (en) * | 1996-09-27 | 1998-04-21 | Novartis Ag | Salg�n hastal�k ila�lar� (pepticides). |
| DE10111262A1 (en) * | 2001-03-09 | 2002-09-12 | Studiengesellschaft Kohle Mbh | Process for the preparation of vinyl aryl and heteroarylacetic acids and their derivatives |
| WO2002079339A2 (en) * | 2001-03-30 | 2002-10-10 | The Penn State Research Foundation | Metal catalyzed reactions |
| US6858592B2 (en) | 2001-06-29 | 2005-02-22 | Genzyme Corporation | Aryl boronic acids for treating obesity |
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| KR100624238B1 (en) * | 2004-06-22 | 2006-09-19 | 한국화학연구원 | Pharmaceutical composition for prevention and treating of metabolic bone diseases containing alpha-arylmethoxyacrylate derivatives |
| CN103153958A (en) | 2010-07-02 | 2013-06-12 | 先正达参股股份有限公司 | Novel microbiocidal dioxime ether derivatives |
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